This invention relates generally to a light therapy device for activation of medicaments at one or more treatment sites within a living body, and more specifically, to photodynamic therapy devices adapted to reduce dislodgment risk over long treatment periods and enable a patient to be ambulatory without interruption of the therapy.
Photodynamic therapy (PDT) is a two-step treatment process which has been found to be effective in destroying a wide variety of cancers. PDT is performed by first systemically or topically administering a photosensitizer compound, and subsequently illuminating a treatment site with light in a waveband, which corresponds to an absorption waveband of the photosensitizer. The light energy activates the photosensitizer compound, causing it to destroy the diseased tissue.
Numerous systems have been proposed to effectively deliver the activating light to the treatment site. Examples of such systems can be found in U.S. Pat. No. 5,519,534 issued May 21, 1996 to Smith, et al., U.S. Pat. No. 5,344,434 issued Sep. 6, 1994 to Talmore, and U.S. Pat. No. 4,693,556 issued Sep. 15, 1987 to McCaughan. The systems disclosed in these patents generally comprise a laser light source coupled to a proximal end of a flexible biocompatible optical fiber having a distal end adapted to be positioned within the body of a patient, either inside or adjacent to an internal treatment site. The optical fiber conducts and guides activating light from the laser light source to the treatment site at the distal end of the optical fiber. A diffuser enclosing the distal end of the optical fiber diffuses the light, and thus delivers the light to the treatment site at a uniform intensity to effect activation of the photosensitizer compound. In these systems, the diffuser may comprise a sphere positioned on the distal end of the fiber and having an inner partially reflective surface that aids in diffusing light transmitted through the sphere. Other light delivery devices can be found, for example, in U.S. Pat. No. 5,709,653 issued Jan. 20, 1998 to Leone, U.S. Pat. No. 5,700,243 issued Dec. 23, 1997 to Nariso, and U.S. Pat. No. 5,645,562 issued Jul. 8, 1997 to Hann, et al., and U.S. Pat. No. 4,998,930 issued Mar. 21, 1991 to Lundahl. While disclosing systems that are generally similar to the aforementioned systems, these references described diffusers that have an added component. The diffusers of these devices either alternatively or additionally incorporated transparent balloons mounted coaxially around the distal end of the optical fiber. Once the distal end is positioned at the treatment site, the balloon may be inflated in order to increase the area of the treatment site which will be exposed to the activating light, and in some cases, to effect or at least aid in the diffusion of the activating light. Once the light therapy provided by delivery of the light to the treatment site is completed, the balloon may be deflated, and the optical fiber removed from the body of the patient.
A conventional PDT treatment is of very short duration, on the order of minutes, and is typically used to treat superficial and small volume lesions. In order to apply PDT successfully against large lesions, which may be located subcutaneously, more extended treatment sessions must be undertaken. Extending the time of treatment overcomes tumor resistance and enables the extent of the treatment site to be greatly enlarged, thus allowing effective therapy of a much greater tumor volume. Indeed, destruction of a large tumor volume by extended duration PDT has been demonstrated in a clinical treatment. The treated patient suffered from a very large retroperitoneal tumor, which had eroded through the skin. The protruding tumor was treated by inserting multiple light emitting probes, such as is described in commonly assigned U.S. Pat. No. 5,445,608, into the substance of the tumor. The probes were energized for more than forty hours after orally administering a dose of a photosensitizer called aminolevulinic acid. This treatment resulted in destruction of just under one-half kilogram of tumor mass over the ensuing four weeks.
While adequate for some applications, the lasers, other high-powered light sources, and optical fibers in current use for administering PDT to a treatment site suffer several drawbacks related to safety and their inability to accommodate the extended sessions necessary to effectively treat large tumors. First, high-powered sources such as dye lasers, laser diodes, large light emitting diode (LED) arrays, incandescent sources, and other electroluminescent devices are not efficient in converting electrical energy into light energy. They generate significant amounts of heat, and consume a substantial amount of electrical power. Prolonged use of high intensity light sources can lead to inadvertant tissue damage due to the effect of the high intensity light. Further, certain of these devices, e.g. laser light sources, generate sufficient heat that they must be cooled while activated. The need for cooling necessitates the incorporation of additional hardware such as fans cooling units that draw additional power from the main power supply.
Second, the amount of power consumed by high intensity light sources requires that they be supplied with power from an alternating current (AC) line power source. Movement by the patient or attendance efforts by hospital personnel during the treatment period that cause the patient to move can inadvertently disconnect or damage the power cord, not only interrupting the treatment, but also creating a risk of electric shock. Further, being tethered to a substantially fixed power source limits the application of optical extended treatments, inasmuch as the patient will invariably need to move or be moved during the treatment period. Movement of the patient will likely cause the treatment to be interrupted and thus, render it less effective.
Third, none of the prior art techniques for rendering PDT to an internal treatment site through an optical fiber provides an anchoring mechanism to effectively secure the optical fiber and its distal end within the body of the patient at the treatment site. Any movements by the patient or attendance efforts by hospital personnel during the treatment period could inadvertently pull or dislodge the optical fiber unless it is secured in place. In many cases, while it is easy to disconnect a power cable from a light source to allow the patient to temporarily move about before resuming treatment, it is not practical to remove the optical fiber from the patient""s body at that time, as well. Instead, the optical fiber must remain in place while the patient moves about. Without an effective mechanism for securing the optical fiber in the patient""s body and at the treatment site while the patient moves, the risk of tissue damage is increased by such activity. Not only can the tissue be torn or severe bleeding occur when the patient moves, but if the dislodgement is not so severe, that it is noticed, the distal end of the optical fiber can be displaced away from the treatment site, so that light is delivered to the wrong area in the patient""s body, resulting in possibly severe and unwanted destruction of normal tissue.
Fourth, the methodology of short duration high intensity illumination has drawbacks when applied to treat moderate to large size tumors. These drawbacks include depletion of oxygen necessary for the photodynamic destruction of the tissue that has absorbed the photosynthesizer, incomplete activation of the circulating photosensitizer, mis-timing of the illumination session so that the light therapy is not administered during the peak concentration of the photosensitizer drug in the tumor, and the possible recovery of sub-lethally injured tumor cells, which were not completely destroyed due to the short treatment time.
Currently, PDT procedures using laser light sources may be performed during an operation in which a treatment site is surgically exposed, and as such, the period available for administering light therapy is approximately one to two hours at most. The extent of tumor necrosis resulting from such an illumination period is on the order of 1 to 2 centimeters in a zone radially surrounding the optical fiber. Thus, several devices have been developed in an attempt to increase the duration of PDT treatments, to enable the light therapy to continue after an incision in a patient undergoing surgery has been closed. For example, a number of solid state laser devices have been developed for administering PDT that are semi-portable. However, these devices are large, heavy, and must be transported on wheeled carts or other movable furniture. Such xe2x80x9cdesktopxe2x80x9d or semi-portable devices suffer from the drawbacks enumerated above if employed for prolonged PDT treatment periods lasting hours. Furthermore, such light sources must remain connected to the wall power plug by power cables, and the optical fibers through which light produced by the laser is directed to an internal treatment site are prone to dislodgment.
Another light source device, disclosed in U.S. Pat. No. 5,616,140 issued Apr. 1, 1997 to Prescott, can be powered by rechargeable batteries and thus, can be worn by the patient. However, because this device generates only low power laser light, and is not designed to be coupled to optical fibers for directing the light it produces to an internal treatment site, its use is limited to superficial light therapy, e.g., to treating skin lesions. High power lasers currently used for PDT require cooling hardware, and a corresponding power source. Due to weight and size considerations, it is clearly not practical for a patient to move about pushing a high power laser, a cooling unit, and battery power supplies for the equipment sufficient to provide for a prolonged treatment session.
Accordingly, there is a need for a PDT system to administer light therapy, which reduces the risk of optical fiber dislodgement and allows a patient to move about without interruption of the PDT therapy over treatment periods lasting hours.
Citation of the above documents is not intended as an admission that any of the foregoing is pertinent prior art. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents. Further, all documents referred to throughout this application are incorporated in their entirety by reference herein.
The present invention is directed to a PDT device enabling efficacious treatment of relatively large tumors that are currently not treatable using conventional PDT delivery systems and methodologies and is specially adapted to reduce the risk of dislodging an optical fiber from a treatment site and when the patient moves about. The patient can thus be ambulatory without interruption of the light therapy over long treatment periods. In a preferred embodiment, the present invention comprises a belt or harness that supports and secures a lightweight rechargeable battery and a cold cathode fluorescent (CCF) tube powered thereby to a patient. The CCF tube is coupled to a proximal portion of the optical fiber. A distal portion of the optical fiber is provided with means for diffusing light as it exits the optical fiber. The distal portion of the fiber is adapted to be positioned at a treatment site within a patient""s body by a medical practitioner. A balloon disposed at a distal end of the optical fiber can be inflated after the insertion of the optical fiber within the patient""s body, to secure the distal portion of the fiber within the tissue at the treatment site; the balloon is deflated prior to the removal of the optical fiber, once administration of the light therapy is completed.
The present invention overcomes the limitations of the prior art PDT delivery devices in several respects. First, the use of a CCF tube provides increased effectiveness and efficiency compared to laser light sources. Light energy losses due to coupling of the light source to the optical fiber are minimized by employing a parabolic reflector and lens to focus the light into the proximal portion of the optical fiber. It is possible to obtain a greater zone of necrosis using non-laser light delivered to the tumor mass over a longer period of time, for example, 40 hours. Therefore, a CCF tube is preferred over other light sources, such as solid laser diodes, fiber lasers, LEDs, incandescent sources, halogen sources, polymeric luminescent devices or other electroluminescent devices, because CCF tube is generally more efficient in converting electrical power to light energy. As such, it not only generates a minimal amount of heat, but also consumes a minimal amount of power, thereby eliminating the need for cooling fans and large or substantially fixed power supplies. In contrast, the alternative light sources listed above suffer from lower conversion efficiencies, generate more heat, and require greater amounts of electrical power.
A second advantage is that the use of a CCF tube allows the present invention to be powered by a portable power supply that employs widely available and commonly used rechargeable batteries such as lithium ion, nickel metal hydride, and nickel cadmium rechargeable batteries, which are lightweight and inexpensive. In contrast, the need for at least some of the other types of light sources to be accompanied by cooling fans, and even cooling systems (with the need for an additional power supply to run the cooling system), makes it impractical for them to be adapted to a portable system, because they are too bulky, weigh too much, and are too expensive. It is not a trivial advantage for the present invention to be readily portable and free from being continuously linked to a stationary or permanent power source. As the present invention can be carried about by the patient on a belt or harness, there are no power cables, which can be severed or pulled from a fixed power source due to inadvertent movements by the patient. Thus, the risk of treatment interruption and electric shock is minimized. More importantly, the patient will be able to undergo optimal extended treatment sessions, as the patient will be able to move freely or be moved without interruption of the treatment. The ability of a CCF tube to be formed into various compact shapes, including xe2x80x9cUxe2x80x9ds, coils, spirals, and elongate forms, further facilitates the efficient administration of light to various correspondingly shaped treatment sites by the present invention and permits the system to be worn and transported by the patient easily and comfortably.
A third advantage provided by the present invention is that it enables a CCF tube to be easily coupled in light channeling relation to the proximal portion of at least one biocompatible optical fiber. The biocompatible optical fiber is flexible not only inasmuch as its distal portion can be easily positioned within the tissue of the patient at a treatment site, but also because it can accommodate movement of surrounding tissue associated with patient respiration and ambulation. A parabolic mirror positioned in partially surrounding relation to the CCF tube and a focusing lens positioned between the CCF tube and the proximal portion of the fiber cooperate to channel light into the proximal portion of the fiber. Specifically, the parabolic mirror reflects light from the CCF tube onto the focusing lens which focuses the light into the proximal portion of the optical fiber. After the light travels through the optical fiber, it is diffused at the distal portion of the optical fiber by a diffuser of the types that are well known and documented in the art. The diffusion of the light emitted from the distal portion of the optical fiber enables the light to be administered more uniformly to the treatment site to activate the photosensitive compound previously administered. The length of the optical fiber is preferably limited to that necessary to reach the treatment site, in order to minimize light loss along the length of the optical fiber. The outer coating of the optical fiber is preferably opaque to light, in order to prevent light leaking from the optical fiber activating any photosensitizer absorbed by normal tissue along the length of the fiber. Additional biocompatible optical fibers may be connected to the parabolic mirror and focusing lens coupling the light into the proximal portions of the optical fibers or alternatively, may be spliced into the biocompatible optical fiber into which the light is focused.
A fourth advantage of the present invention over the prior art devices is that it optionally includes anchoring means for securing the optical fiber and particularly, its distal portion within the body of the patient at the treatment site. The balloon mounted to the distal end of the optical fiber can be inflated with a pressurized fluid such as air that flows through a lumen that extends substantially parallel to and which is disposed within or adjacent to the optical fiber. This lumen is thus maneuverable with the optical fiber. The lumen runs substantially the length of the optical fiber, from the pressurized fluid source that is external to the patient""s body to the balloon at the distal end of the optical fiber. After positioning the distal portion of the fiber within the tissue of the patient at the treatment site, the balloon is inflated to secure the distal end of the optical fiber in the tissue. The inflated balloon also tamponades any bleeding, which may occur at the distal end of the optical fiber during its insertion. Thus, any movement by the patient during the treatment will not dislodge the optical fiber or its distal portion because the balloon anchors the optical fiber in place. Similarly, movement of the distal portion of the optical fiber will thus be avoided, preventing light from being administered to healthy tissue that has absorbed the photosensitizer. Overall, the risk of damage to normal tissue is minimized, and the need for the patient to interrupt treatment before moving about is eliminated. Once treatment is complete, the balloon is deflated to facilitate removal of the optical fiber from the patient""s body. It should be noted that for some applications, the distal portion of the optical fiber should preferably abut, rather than be embedded in the treatment site. This may be the case where, for example, it is undesirable or difficult to penetrate the tumor or diseased tissue. In such a situation, the balloon may be positioned at an intermediate point along the length of the optical fiber and/or in coaxially surrounding relation to the optical fiber, rather than at its distal end.
The above features and advantages of the present invention will be better understood upon a reading of the following detailed description with reference to the accompanying drawings.